This project is designed to develop radioimmunoassays (RIA) for the measurement of plasma levels of the tricyclic antidepressants. Tricyclic plasma levels vary widely among patients receiving the same dose of drug and the clinical response of individual patients may be related to plasma levels of the tricyclic. Present analytical methods are not suitable for the routine clinical measurement of plasma tricyclics. The radioimmunoassay we propose will provide a sensitive, specific, precise, rapid and convenient method for the daily measurement of large numbers of samples on small volumes of plasma, serum or saliva. In addition to developing RIA's for measuring the total level of tricyclics in plasma we are also developing methods for measuring the unbound level of tricyclic in plasma since it is the unbound fraction of drug in plasma rather than the total plasma level, which represents the pharmacologically active portion of the drug.